On May 14, 2020 Targovax ASA (OSE: TRVX), a clinical stage immuno-oncology company developing oncolytic viruses to target hard-to-treat solid tumors, reported that an abstract relating to the dose escalation part of the ONCOS-102 and durvalumab trial in primary ovarian and colorectal cancer that has spread to the peritoneum has been selected for presentation at a Poster Discussion Session during ASCO (Free ASCO Whitepaper) 2020 (Press release, Targovax, MAY 14, 2020, View Source [SID1234558099]).

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The study is an open label, exploratory phase I/II trial assessing the intra-peritoneally delivered ONCOS-102 in combination with systemically administered checkpoint inhibitor durvalumab in patients with platinum-resistant ovarian or colorectal cancers that have metastasized to the peritoneal cavity. The trial is designed with a dose-escalation phase assessing three different dosing levels, followed by an expansion phase with a total of up to 78 patients enrolled into separate groups of ovarian and colorectal cancer.

In the ASCO (Free ASCO Whitepaper) abstract, safety, immune activation and clinical response data for the three dose escalation cohorts will be presented. A total of 17 patients were enrolled, 4 in cohort A (low dose), 5 in cohort B (middle dose) and 8 in cohort C (high dose). No dose-limiting toxicities were observed, and the combination had an acceptable safety profile. Therefore, the high-dose level was selected for the expansion phase of the trial, which is currently enrolling patients. Preliminary analyses indicate that the treatment is triggering immune activation and has clinical activity, which were more pronounced in cohort B and C.

Dr. Magnus Jäderberg, Chief Medical Officer of Targovax, said: "We are very proud that ONCOS-102 was chosen as the oncolytic virus of choice for this trial and we are equally pleased that the scientific committee has selected our ONCOS-102 and durvalumab combination abstract for a poster discussion at the upcoming ASCO (Free ASCO Whitepaper) meeting. Although it is too early in the trial to interpret the clinical data, we are happy to have moved into the expansion phase following successful completion of the dose escalation phase. This is an important clinical trial as it addresses a disease with a very high unmet medical need while potentially opening up intra-peritoneal administration as an alternative delivery route for ONCOS-102."

Poster discussion sessionAbstract title:

Developmental Therapeutics-ImmunotherapyPhase I/II study to evaluate systemic durvalumab + intraperitoneal (IP) ONCOS-102 in patients with peritoneal disease who have epithelial ovarian (OC) or metastatic colorectal cancer (CRC): Interim phase I clinical and translational results.

Date / time:

29 May 2020, 8-11AM CDT

Abstract / Poster:

3017 / 81

The abstract can be found here View Source

The trial is a collaboration between Targovax, AstraZeneca, Cancer Research Institute (CRI) and Ludwig Cancer Research.

On May 14, 2020 Milestone Pharmaceuticals Inc. (Nasdaq: MIST), a biopharmaceutical company focused on the development and commercialization of innovative cardiovascular medicines, reported financial results for the first quarter ended March 31, 2020 and provided a clinical and corporate update (Press release, Milestone Pharmaceuticals, MAY 14, 2020, View Source [SID1234558098]).

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"While the NODE-301 trial of etripamil for patients with paroxysmal supraventricular tachycardia (PSVT) did not meet its primary endpoint over the five hour observation period, we are encouraged by the topline data from the trial. With a favorable safety and tolerability profile as well as efficacy signals observed across earlier time points, topline results from NODE-301 reinforce our belief that etripamil has the potential to serve as the first self-administered therapy for the rapid termination of supraventricular tachycardia (SVT) episodes in the at-home setting," said Joseph Oliveto, President and Chief Executive Officer of Milestone Pharmaceuticals. "We look forward to working with regulators to determine next steps, with the goal of ensuring that etripamil is able to realize its full potential in patients with PSVT. In parallel, we continue to execute on the balance of the NODE program, including NODE-301B as well as open-label safety studies NODE-302 and NODE-303."

Recent Updates

Reported Topline Results from Phase 3 NODE-301 Trial, Anticipates Regulatory Update in Early 3Q 2020. In March 2020, Milestone reported topline results from its Phase 3, multicenter, randomized, double-blind, placebo-controlled NODE-301 trial of its investigational new drug, etripamil nasal spray, the Company’s novel short-acting calcium channel blocker, in patients with PSVT. Despite early activity, including the conversion of 61% of etripamil patients vs. 45% of placebo patients by 45 minutes (p=0.02), a time period consistent with etripamil’s known pharmacological activity, the study did not achieve its primary endpoint of time to conversion of SVT to sinus rhythm compared to placebo over the five hour period following study drug administration (p=0.12). The small number of placebo patients and prolonged efficacy measurement period was found to have confounded the results. The study did demonstrate statistically significant improvements in favor of etripamil over placebo in the important secondary endpoint of patient reported treatment satisfaction. Milestone believes the safety and tolerability data from the NODE-301 study will be supportive of at-home use of etripamil, with adverse events consistent with those observed in prior trials.

The Company is determining next steps with regulators and expects to provide an update early in the third quarter of 2020. The Company’s full PSVT clinical program, including NODE-301B, NODE-302 and NODE-303, remains ongoing. NODE-301B, which was designed to collect double-blind data from randomized patients who had not yet experienced an event after the NODE-301 trial reached its target number of adjudicated SVT events, is expected to be analyzed separately as a second safety and efficacy data set.
Reduction in Operating Expenses. Milestone expects to reduce planned operating expenses by 20-25% in order to focus its efforts on an optimized clinical development pathway for etripamil that will be determined following regulatory feedback. The cuts will primarily affect pre-commercialization activities. The goal of the operating cuts is to facilitate an additional efficacy study for etripamil in PSVT and to extend the Company’s cash runway. The Company will update its cash runway guidance after meeting with regulators.
Jeff Nelson Promoted to Chief Operating Officer. In March 2020, Milestone announced the promotion of Jeff Nelson to Chief Operating Officer. Mr. Nelson, who joined the Company in 2018 as Vice President of Program Management, brings to this new role over 15 years of experience in the pharmaceutical and biotech field, working primarily in project management, clinical operations, regulatory affairs, drug supply and distribution and public finance.
First Quarter 2020 Financial Results

As of March 31, 2020, Milestone had cash and cash equivalents of $102 million and 24.6 million shares outstanding.
Research and development expense for the first quarter of 2020 was $11.9 million compared with $7.8 million for the prior year period. The increase in expense was primarily driven by increased clinical development costs and manufacturing and formulation activities supporting its Phase 3 clinical trials.
General and administrative expenses for the first quarter of 2020 were $2.7 million compared with $1.0 million for the prior year period. The increase was driven by additional headcount, professional fees and increased insurance costs.
Commercial expense for the first quarter of 2020 was $2.2 million and remained consistant with the prior year period.
For the first quarter of 2020, operating loss was $16.8 million compared to $10.9 million for the prior year period.
About Paroxysmal Supraventricular Tachycardia

Paroxysmal supraventricular tachycardia (PSVT) is a rapid heart rate condition characterized by intermittent episodes of supraventricular tachycardia (SVT) that start and stop suddenly and without warning. Episodes of SVT are often associated with symptoms including palpitations, sweating, chest pressure or pain, shortness of breath, sudden onset of fatigue, lightheadedness or dizziness, fainting, and anxiety. Certain calcium channel blockers have long been approved for the treatment of PSVT as well as other cardiac conditions; however, when calcium channel blockers are used for the termination of SVT episodes, they must be administered intravenously under medical supervision, usually in an emergency department or other acute care setting.

About Etripamil

Etripamil, the Company’s lead investigational product, is designed to be a rapid response therapy for episodic cardiovascular conditions. The novel calcium channel blocker is self-administered via a nasal spray which may shift the current treatment paradigm for many patients with PSVT from the emergency department to the at-home setting. Milestone is conducting a comprehensive development program for etripamil, with Phase 3 trials underway in PSVT, and plans to commence a Phase 2 proof-of-concept trial in atrial fibrillation patients with rapid ventricular rate, with subsequent studies expected in other conditions where calcium channel blockers are used.

On May 14, 2020 Agendia, Inc., a world leader in precision oncology for breast cancer, reported that they will present new data from its ongoing clinical research evaluating the MammaPrint and BluePrint genomic tests at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (ASCO) (Free ASCO Whitepaper), taking place virtually May 29-May 31, 2020 (Press release, Agendia, MAY 14, 2020, View Source [SID1234558097]).

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Data will underscore Agendia’s mission to help guide the diagnosis and personalized treatment of breast cancer for patients throughout their treatment journey. This data builds upon existing clinical research that demonstrates the efficacy of Agendia’s MammaPrint and BluePrint testing to consistently inform optimal treatment planning.

Specific data selected for presentation will include: an evaluation of the concordance between human epidermal growth factor receptor 2 (HER2) status as put forth by the 2018 ASCO (Free ASCO Whitepaper)/CAP guideline classification and BluePrint genomic testing; an examination of specific oncogenes and their correlation with risk scoring and molecular subtyping results; the ability of a chemokine gene score and MammaPrint to predict pathologic complete response (pCR) following neoadjuvant chemotherapy.

Two other poster presentations will feature additional data sets from Agendia’s ongoing multicenter, prospective, observational trial for patients with Stage I, II, and III breast cancer (FLEX). Researchers will share data from FLEX analyses evaluating triple negative breast cancers (TNBC), as well as the clinical estrogen receptor status of Basal-Type tumors based on self-reported patient ethnicities, new gene expression profiles and investigator-initiated protocols in early stage breast cancer.

"Our MammaPrint and BluePrint assays have demonstrated the ability to uniquely guide the practice of precision oncology in helping patients and their healthcare providers create the most targeted and appropriate treatment plan," says William Audeh, MD, MS, chief medical officer at Agendia. "We continue to investigate biologic drivers of breast cancer to help reduce uncertainty when choosing a treatment regimen and these latest data sets offer additional clinical insights that we believe can translate to improved patient outcomes."

Following are details of the five Agendia abstracts that have been accepted for poster presentations at the 2020 ASCO (Free ASCO Whitepaper) Annual Congress:

TNBC subtype and clinical estrogen receptor status of genomically basal breast tumors in Caucasian, African American, and Latin American patients
Authors: Kaklamani, V., et al.
Session: Breast Cancer—Local/Regional/Adjuvant
Abstract #: 556

The FLEX real world data platform explores new gene expression profiles and investigator-initiated protocols in early stage breast cancer
Authors: D’Abreo, N., et al.
Session: Health Services Research and Quality Improvement
Abstract #: TPS7088

High Risk breast cancer genes at 8q22-24 and their role in over 5000 patients evaluated with the 70-gene risk of recurrence assay
Authors: Diab, S., et al.
Session: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology
Abstract #: 3569

Adding precision to 2018 ASCO (Free ASCO Whitepaper)/CAP HER2 testing guidelines in breast cancer with genomic profiling
Authors: Brufsky, A., et al.
Session: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology
Abstract #: 3570

12-chemokine gene expression score in breast cancer patients treated with neoadjuvant chemotherapy
Authors: Soliman, H., et al.
Session: Breast Cancer—Local/Regional/Adjuvant and Developmental Therapeutics—Immunotherapy
Abstract #: 591

In addition, the European Organisation for Research and Treatment of Cancer (EORTC) will be presenting nearly nine year follow-up data from the landmark MINDACT study. The independent trial, originally published in the New England Journal of Medicine in 2016, confirmed the clinical utility of MammaPrint as a prognostic tool in identifying genomic Low Risk patients who do not significantly benefit from chemotherapy.

Please follow us on our Twitter, Facebook and LinkedIn pages for unique content we will be sharing throughout ASCO (Free ASCO Whitepaper).

The ASCO (Free ASCO Whitepaper) 2020 virtual program can be found in our Resources section of our website.

On May 14, 2020 Tolero Pharmaceuticals, Inc., a clinical-stage company focused on developing novel therapeutics for hematological and oncological diseases, reported that the first patient has been dosed with a one-hour dosing schedule for investigational agent alvocidib, a potent CDK9 inhibitor, administered in sequence after azacitidine, in the expansion of the Phase 1b/2 Zella 102 study in patients with myelodysplastic syndromes (MDS) (Press release, Tolero Pharmaceuticals, MAY 14, 2020, View Source [SID1234558096]).

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The Zella 102 study is being conducted in patients with previously untreated MDS and patients with MDS who have received fewer than six cycles of treatment with a hypomethylating agent. The initial study design was to evaluate the safety and efficacy of alvocidib using a 30-minute bolus followed by a four-hour intravenous infusion (IVI), in combination with decitabine. An amendment was made to the study design to include treatment with azacitidine, in sequence before a one-hour infusion of alvocidib.

"We are pleased that this study now includes both standard of care hypomethylating agents for patients with myelodysplastic syndromes. In addition, the expansion of this study offers an alternative alvocidib dosing schedule, which reduces the amount of time patients spend in infusion," said David J. Bearss, Ph.D., Chief Executive Officer, Tolero Pharmaceuticals, and Chief Scientific Officer and Global Head of Research, Global Oncology. "Preclinical research suggests that treatment with hypomethylating agents may sensitize MDS blast cells to suppression of MCL-1 through alvocidib. We look forward to building our understanding of the potential role of alvocidib in this patient population."

MDS is a form of cancer that can occur when cells in the bone marrow are abnormal and create defective blood cells, which often die earlier than normal cells. In one of three patients, MDS can progress into AML, a rapidly growing cancer of bone marrow cells.1

About the Zella 102 Study

The Zella 102 study is an open-label, dose-escalation Phase 1b/2 study evaluating the safety and efficacy of alvocidib, when administered in sequence after either decitabine or azacitidine, in patients with previously untreated MDS and patients with MDS who have received fewer than six cycles of treatment with hypomethylating agents. The primary objective of the Phase 1b portion of the study is to determine the maximum tolerated dose and recommended Phase 2 dose of alvocidib, when administered in these regimens. Secondary objectives are to determine the complete response rate and if treatment with alvocidib, administered in sequence after decitabine or azacitidine, results in improvements in transfusion dependence and/or hemoglobin level.

The primary objective of the Phase 2 portion of the study will be to determine the objective response rate of alvocidib, when administered to untreated patients with de novo or secondary MDS in sequence after a hypomethylating agent, using revised International Working Group (IWG) criteria.

The trial is being conducted at sites in the United States. Additional information on this trial, including comprehensive inclusion and exclusion criteria, can be accessed at www.ClinicalTrials.gov (NCT03593915).

About Alvocidib

Alvocidib is an investigational small molecule inhibitor of cyclin-dependent kinase 9 (CDK9) currently being evaluated in the Phase 2 studies Zella 202, in patients with acute myeloid leukemia (AML) who have either relapsed from or are refractory to venetoclax in combination with decitabine or azacitidine (NCT03969420) and Zella 201, in patients with relapsed or refractory MCL-1 dependent AML, in combination with cytarabine and mitoxantrone (NCT02520011). Alvocidib is also being evaluated in Zella 101, a Phase 1 clinical study evaluating the maximum tolerated dose, safety and clinical activity of alvocidib in combination with cytarabine and daunorubicin (7+3) in newly diagnosed patients with AML (NCT03298984), and Zella 102, a Phase 1b/2 study in patients with myelodysplastic syndromes (MDS) in combination with decitabine or azacitidine (NCT03593915). In addition, alvocidib is being evaluated in a Phase 1 study in patients with relapsed or refractory AML in combination with venetoclax (NCT03441555).

About CDK9 Inhibition and MCL-1

MCL-1 is a member of the apoptosis-regulating BCL-2 family of proteins.2 In normal function, it is essential for early embryonic development and for the survival of multiple cell lineages, including lymphocytes and hematopoietic stem cells.3 MCL-1 inhibits apoptosis and sustains the survival of leukemic blasts, which may lead to relapse or resistance to treatment.2,4 The expression of MCL-1 in leukemic blasts is regulated by cyclin-dependent kinase 9 (CDK9).5,6 Because of the short half-life of MCL-1 (2-4 hours), the effects of targeting upstream pathways are expected to reduce MCL-1 levels rapidly.5 Inhibition of CDK9 has been shown to block MCL-1 transcription, resulting in the rapid downregulation of MCL-1 protein, thus restoring the normal apoptotic regulation.2

On May 14, 2020 Citius Pharmaceuticals, Inc. (Nasdaq: CTXR), a specialty pharmaceutical company focused on adjunctive cancer care and critical care drug products, reported that it has entered into definitive agreements with several institutional and accredited investors for the purchase of 7,058,824 shares of its common stock, at a purchase price per share of $1.0625 for gross proceeds of approximately $7.5 million, in a registered direct offering priced at-the-market under Nasdaq rules (Press release, Citius Pharmaceuticals, MAY 14, 2020, View Source [SID1234558095]). Additionally, Citius has also agreed to issue to the investors unregistered warrants to purchase up to 3,529,412 shares of its common stock. The closing of the offering is expected to take place on or about May 18, 2020, subject to the satisfaction of customary closing conditions.

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H.C. Wainwright & Co. is acting as the exclusive placement agent for the offering.

The warrants have an exercise price of $1.00 per share, will be immediately exercisable, and will expire five and one-half years from the issue date.

Citius intends to use the net proceeds from the offering for general corporate purposes, including clinical trial expenses, research and development expenses, manufacturing expenses and general and administrative expenses.

The shares of common stock described above (but not the warrants or the shares of common stock underlying the warrants) are being offered pursuant to a "shelf" registration statement (File No. 333-221492) filed with the Securities and Exchange Commission (SEC) and declared effective on December 15, 2017. Such shares of common stock may be offered only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement. A final prospectus supplement and the accompanying prospectus relating to the offering of the shares of common stock will be filed with the SEC and be available at the SEC’s website at www.sec.gov. Electronic copies of the prospectus supplement and the accompanying prospectus relating to the offering of the shares of common stock may also be obtained, when available, by contacting H.C. Wainwright & Co., LLC at 430 Park Avenue, 3rd Floor, New York, NY 10022, by emailing [email protected] or by calling 646-975-6996.

The warrants described above were offered in a private placement under Section 4(a)(2) of the Securities Act of 1933, as amended (the "Act"), and Regulation D promulgated thereunder and, along with the shares of common stock underlying the warrants, have not been registered under the Act, or applicable state securities laws. Accordingly, the warrants and underlying shares of common stock may not be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Act and such applicable state securities laws.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any of the securities described herein, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.